1. Field of Invention
The present invention relates to an apparatus and a method for producing particles using supercritical fluid and, more particularly, to an apparatus and a method for producing particles using a supercritical fluid and a secondary mixing assembly.
2. Description of Related Art
Particles having very small diameters and a narrow range of particle sizes are desired for a variety of end-use applications such as, for example in the production of pharmaceutical compositions. Several processes have been developed over the years to produce single-component and multi-component (i.e., composite) particles utilizing the enhanced mass-transfer properties and generally benign nature of supercritical fluids, near-critical fluids and compressed gases. Unfortunately, it has been very difficult to obtain small sized particles (diameters less than 100 μm) with a narrow particle size distribution using such processes.
One such supercritical fluid processing technique is known in the art as Particles from Gas-Saturated Solutions (PGSS). In the conventional PGSS technique, a compound or a mixture of compounds is plasticized with a supercritical fluid to form a plasticized mass or “melt” that is then expanded across a pressure drop. The rapid decrease in pressure causes the supercritical fluid to change into a gas phase, which results in supersaturation and ultimately precipitation of the compound or mixture of compounds as particles.
Particle agglomeration is frequently problematic in conventional PGSS processing. During particle formation, bridges can form between growing particles, which can lead to large differences in particle size and wide particle size distributions. Furthermore, particles produced by conventional PGSS processing techniques tend to exhibit a broad size distribution in sizes above 100 μm and tend to be non-uniform (i.e., irregular) in shape.
Another problem typically associated with the conventional PGSS process is that mixtures of compounds tend to separate as they pass across the pressure drop. The separation phenomenon can make it difficult to produce uniform composite particles, and can actually result in the production of an undesirable blend of particles that are formed of one material or the other, but not both materials. Homogeneous composite polymer/drug micro-spheres and uniform coated particles are particularly difficult to produce using the conventional PGSS process.
The particle agglomeration problem typically encountered with the PGSS process is exacerbated when the melt comprises one or more compounds that exhibit a relatively high melt viscosity. Polymers, which are often used as carriers or excipients for pharmaceutical compositions, tend exhibit a relatively high viscosity in such melts. Because of the undesirable viscosity and concentration of the polymer relative to the supercritical fluid used to form the melt, efficient particle dispersion is difficult to obtain. Furthermore, the process is often plagued with nozzle clogging and poor particle coating efficiency. Demixing and poor wetting between the carrier and biologically active agents further reduces the coating efficiency and can lead to an undesirable non-homogeneous particle coating.